Early onset or syndromic epilepsy

Gene: PTPN23

Comment on phenotypes: Added disease association from OMIM.

Created: 15 Jul 2020, 2:20 p.m. | Last Modified: 15 Jul 2020, 2:20 p.m.

Panel Version: 2.123

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

No OMIM entry re disease. HGMD Pro - 6 variants listed. Alzami et al 2015 - hom missense variant in a child with global dev delay, epilepsy and brain atrophy. Trujillano et al, hom missense variant in a proband with a similar phenotype. Sowada et al, 2017 - novel compound het variant in a non consang proband - similar clinical picture as before - nonsense and a missense. Also reviewing patient from Alzami et al. 3D structure suggests the missense variant would have an effect. Smigiel et al, 2018 - proband -non consang - similar phenotype - compound het (missense and a fs) - functional work support pathogenicity. Rare but all patients with disease do have epilepsy as part of there phentoype and structural/functional studies back this up so far.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
epileptic encephalopathy

Publications

• 29090338

Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen, at least 5 variants reported in 3 unrelated cases, together with functional studies and knock-out mouse model. PMID 25558065, first report of PTPN23 homozygous variant (NM_015466.2:c.3995G>T:p.R1332L) in third child of first cousin parents (older sibs died in infancy); 5 year old boy with developmental delay, cerebral palsy, seizure disorder and gastroesophageal reflux disease. PMID: 29899372 reports clinical phenotype of recessive PTPN23 variants ( c.1902C>G (p.(Asn634Lys)) and c.2974delC (p.(Leu992Tyrfs*168)) in a compound heterozygous case with pathogenicity substantiated by functional studies. PMID 29090338 c.3586C>T (p.Arg1196*) and c.1595C>T (p.Pro532Leu) in compound heterozygous case together with embryonic lethality in a PTPN23 knock-out mouse model.

Created: 31 Jul 2018, 11:02 a.m.

Comment on phenotypes: phenotype includes severe developmental delay, epilepsy, cortical blindness, hypomyelination and brain atrophy on MRI (PMID 29899372)

Created: 31 Jul 2018, 10:51 a.m.